In the field of gene therapy, one of the most actively studied areas is gene transfer for hematopoietic stem cells. Despite early achievements using murine model system, clinical success with human stem cell gene transfer has been virtually non-existent. One likely difficulty is that stem cells are thought to be deeply quiescent, and standard retroviral vectors are known to require active replication in order to transduce target cells. Recently, it has been shown that lentiviral vectors (a subfamily of the retrovirus group), are capable of infecting non-dividing cells. Moreover, transduction has been shown to be efficient and applicable to a wide range of mammalian tissue types. Consequently, in this proposal, we describe a plan for determining the utility of lentiviral vectors for transduction Of primitive non-dividing human hematopoietic cells. If such vectors can successfully infect quiescent stem cells, it should lead to the development of a unique and important commercial product- a gene therapy vehicle for human hematopoietic stem cells. We predict such a product would have immediate utility for numerous gene therapy applications, both within the hematopoietic system, as well as for other human tissues. PROPOSED COMMERCIAL APPLICATION: A gene transfer vehicle capable of stable integration in non-dividing cells would vastly expand the gene therapy potential of retroviral vectors. This type of vector would have immediate applicability for virtually any somatic tissue, and provide a means to address numerous human disorders (e.g Hemophilia, Parkinson's Disease, Sickle Cell Anemia, Cystic Fibrosis, etc.